Dataset Information

Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma: A Feasibility Study.

ABSTRACT:

Purpose

Rhabdomyosarcomas (RMS) are rare neoplasms affecting children and young adults. Efforts to improve patient survival have been undermined by a lack of suitable disease markers. Plasma circulating tumor DNA (ctDNA) has shown promise as a potential minimally invasive biomarker and monitoring tool in other cancers; however, it remains underexplored in RMS. We aimed to determine the feasibility of identifying and quantifying ctDNA in plasma as a marker of disease burden and/or treatment response using blood samples from RMS mouse models and patients.

Methods

We established mouse models of RMS and applied quantitative polymerase chain reaction (PCR) and droplet digital PCR (ddPCR) to detect ctDNA within the mouse plasma. Potential driver mutations, copy-number alterations, and DNA breakpoints associated with PAX3/7-FOXO1 gene fusions were identified in the RMS samples collected at diagnosis. Patient-matched plasma samples collected from 28 patients with RMS before, during, and after treatment were analyzed for the presence of ctDNA via ddPCR, panel sequencing, and/or whole-exome sequencing.

Results

Human tumor-derived DNA was detectable in plasma samples from mouse models of RMS and correlated with tumor burden. In patients, ctDNA was detected in 14/18 pretreatment plasma samples with ddPCR and 7/7 cases assessed by sequencing. Levels of ctDNA at diagnosis were significantly higher in patients with unfavorable tumor sites, positive nodal status, and metastasis. In patients with serial plasma samples (n = 18), fluctuations in ctDNA levels corresponded to treatment response.

Conclusion

Comprehensive ctDNA analysis combining high sensitivity and throughput can identify key molecular drivers in RMS models and patients, suggesting potential as a minimally invasive biomarker. Preclinical assessment of treatments using mouse models and further patient testing through prospective clinical trials are now warranted.

SUBMITTER: Ruhen O

PROVIDER: S-EPMC9616639 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma: A Feasibility Study.

Ruhen Olivia O Lak Nathalie S M NSM Stutterheim Janine J Danielli Sara G SG Chicard Mathieu M Iddir Yasmine Y Saint-Charles Alexandra A Di Paolo Virginia V Tombolan Lucia L Gatz Susanne A SA Aladowicz Ewa E Proszek Paula P Jamal Sabri S Stankunaite Reda R Hughes Deborah D Carter Paul P Izquierdo Elisa E Wasti Ajla A Chisholm Julia C JC George Sally L SL Pace Erika E Chesler Louis L Aerts Isabelle I Pierron Gaelle G Zaidi Sakina S Delattre Olivier O Surdez Didier D Kelsey Anna A Hubank Michael M Bonvini Paolo P Bisogno Gianni G Di Giannatale Angela A Schleiermacher Gudrun G Schäfer Beat W BW Tytgat Godelieve A M GAM Shipley Janet J

JCO precision oncology 20221001

<h4>Purpose</h4>Rhabdomyosarcomas (RMS) are rare neoplasms affecting children and young adults. Efforts to improve patient survival have been undermined by a lack of suitable disease markers. Plasma circulating tumor DNA (ctDNA) has shown promise as a potential minimally invasive biomarker and monitoring tool in other cancers; however, it remains underexplored in RMS. We aimed to determine the feasibility of identifying and quantifying ctDNA in plasma as a marker of disease burden and/or treatme ...[more]

PMID: 36265118

Similar Datasets

Project description:Rhabdomyosarcoma (RMS) arises from myogenic precursors that fail to complete muscle differentiation and represents the most frequent soft tissue sarcoma in children. Two major histological subtypes are recognized: alveolar RMS, characterized by a more aggressive behavior and a greater proneness to metastasis, and embryonal RMS which accounts for the 80% of cases and carries a better prognosis. Despite the survival of patients with localized tumors has progressively improved, RMS remains a challenging disease especially for metastatic patients and in case of progressive or recurrent disease after front-line therapy. MicroRNAs, a class of small non-coding RNA, have emerged as crucial players in cancer development and progression, and their detection in plasma (circulating miRNAs) represents a promising minimally invasive approach that deserve to be exploited in clinical practice. We evaluated the utility of circulating miRNAs as diagnostic and prognostic biomarkers in children with RMS profiling miRNAs from plasma of a small cohort of RMS patients and healthy donors (HD) using a qPCR Cancer Panel. An assessment of hemolysis status of plasma using miR-451/miR-23a ratio was performed as pre-analytical analysis. Statistical analysis revealed that miRNAs expression pattern clearly distinguished RMS patients from HD (p < 0.05). Interestingly, plasma levels of muscle-specific miR-206 were found to be significantly increased in RMS patients compared to HD, whereas levels of three potential tumor-suppressor miRNAs, miR-26a and miR-30b/30c, were found lower. Reduced levels of circulating miR-26a and miR-30b/c were further measured in an independent larger cohort of patients (validation set) by digital droplet PCR. In particular, we evidenced that miR-26a absolute plasma levels were associated with fusion status and adverse outcome (p < 0.05). Taken together, these findings demonstrate the potential of circulating miRNA as diagnostic and prognostic biomarker in children affected by this malignancy and enforced the key role of miR-26a in pediatric rhabdomyosarcoma.

Dataset Information

Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma: A Feasibility Study.

Purpose

Methods

Results

Conclusion

Publications

Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma: A Feasibility Study.

Similar Datasets

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